A Comparative Study on the Anti-Inflammatory Activity of Kaempferol and Its O-Glycosides in LPS-Induced RAW264.7 Cells

Kaempferol and its O-glycosides are prevalent dietary flavonoids, yet their comparative anti-inflammatory activities and underlying mechanisms remain poorly defined. This study evaluated the effects of kaempferol and three O-glycosides (K3G, K3R, K3S) on LPS-induced inflammation in RAW264.7 macrophages. Compared with its O-glycosides, kaempferol exhibited markedly stronger anti-inflammatory activity, shown by greater suppression of inflammatory mediators (NO, PGE₂, IL-6, TNF-α) and ROS production. Mechanistically, kaempferol inhibited G0/G1 to S phase progression and attenuated MAPK/NF-κB/IκBα signaling, reducing iNOS and COX-2 expressions. Lipidomics analysis revealed that kaempferol restored LPS-disrupted glycerophospholipid homeostasis and modulated key lipid metabolites. Collectively, these findings highlighted the superior in vitro anti-inflammatory activity of kaempferol relative to its O-glycosides, supporting further investigation of its physiological relevance.